Amine metabolites in cerebrospinal fluid (CSF) are studied in patients to assess neurochemical alterations which may be associated with clinical diagnoses (particularly affective illness, schizophrenia, personality disorders, and alcoholism), biological subgroups, or drug treatment. Probenecid, which inhibits the removal of the metabolites from CSF into the blood, is administered as part of these studies. A study of CSF in normal volunteers is underway both as controls for psychiatric groups and as a separate population for study. In patients with personality disorder, 5-HIAA showed a strong negative correlation with a history of aggression. Low DBH was associated with elevated MMPI profiles and with the development of a psychosis during disulfiram treatment. Several studies explore the use of pretreatment CSF metabolite values in predicting drug response. Neuroendocrine studies suggest heightened serotonergic activity in some unipolar endogenously depressed patients. Physostigmine affects CSF, HVA and MHPG, suggesting a cholinergic influence on dopaminergic and noradrenergic systems. Simpler fluorometric procedures for 5HIAA and HVA were found to correlate highly with the mass spectrometry method, especially in the higher ranges achieved with probenecid.